It is now accepted that the peptides that were originally termed 'gut hormones' are regulatory peptides that are widely distributed in both the enteric and central nervous systems. There is, as yet, no clear understanding of their mode of action. Using two established neurophysiologic models, we propose to characterise the mode of action of regulatory brain-gut peptides by observing the effects of their application to single neurones. The functional role of the peptides will be studied in a rat 'brain-gut' model, in which the responses of single neurones in the dorsal vagal nucleus to stimulation of gastic and enteric mechanoreceptors and chemoreceptors can be defined; the ability of peptides such as opioids, somatostatin, cholecystokinin-octapeptide and vasoactive intestinal peptide to modulate these responses when applied directly by iontophoresis or by pressure ejection from the micro-electrode can be studied. Because such studies do not, however, allow intracellular recording, this model cannot distinguish between neurotransmitter and neuromodulator effects. This distinction can be made using intracellular techniques in the neurones of the myenteric plexus to which peptides have been applied in a similar manner. Rather than use the guinea-pig myenteric plexus preparation that has been used by most workers in this field, we propose to study the rat myenteric plexus and - as available from surgical specimens - the human nyenteric plexus; the choice of these species being the possibility of correlating and interpreting findings in the light of data on the effects of systemic peptides in these species. In addition to the study of peptide agonists in these two systems, we propose to study the effects of putative 'specific' antagonists such as proglumide and dibutrylcGMP. Experience with other systems of the body has shown that effective therapy (such as antihistamines and beta-blockers) requires an understanding of specific control mechanisms, and their chemical modulation. The same is true of the digestive tract.